Diethyl Ether → 6-(5-Acetyl-2-trifluoromethoxy-phenyl)-4-ethyl-2,2,7-trimethyl-4h-benzo[1,4]oxazin-3-one

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Reaction Steps

A solution of Compound 1D (200 mg, 0.49 mmol) in dry 3 mL of dry THF is cooled to −78° C. and treated with a 3M solution of methyl magnesium bromide in diethyl ether (0.17 mL, 0.54 mmol). The reaction was allowed to warm to room temperature, the reaction turned blue when it was complete. The mixture was quenched with 5 mL of a saturated aqueous solution of NH4Cl and passed through a SPE. The crude product was eluted with EtOAc. After removing excess solvent the crude alcohol was then dissolved in 2 mL of dichloromethane and treated with Dess-Martin reagent (250 mg, 0.59 mmol) and stirred at room temperature overnight. The reaction was quenched with 4 mL of saturated sodium thiosulfate solution and 4 mL of saturated sodium bicarbonate solution, the reaction mixture was stirred until clear. The reaction mixture was passed through another SPE and eluted with dichloromethane, removal of solvent yielded crude ketone which was purified with flash chromatography (25% EtOAc/hexane) to yield 95 mg (46%) of the desired product and a white solid. MS (electrospray): mass calculated for C22H22F3NO4, 421.15; m/z found 422.1 [M+H]+.

Provenance & Evidence